Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection

Abstract

All-oral combinations of direct-acting antivirals may improve efficacy and safety outcomes for patients with hepatitis C virus (HCV) infection, particularly those who are poor candidates for current interferon/ribavirin-based regimens. In this open-label, phase 3 study, 135 interferon-ineligible/intolerant and 87 nonresponder patients with chronic HCV genotype 1b infection were enrolled at 24 centers in Japan. Patients received daclatasvir 60 mg once daily plus asunaprevir 100 mg twice daily for 24 weeks. The primary endpoint was sustained virologic response 24 weeks after treatment (SVR24). This study is registered with http://ClinicalTrials.gov (NCT01497834). SVR24 was achieved by 87.4% of interferon-ineligible/intolerant patients and 80.5% of nonresponder (null and partial) patients; rates were similar in cirrhosis (90.9%) and noncirrhosis (84.0%) patients, and in patients with IL28B CC (84.5%) or non-CC (84.8%) genotypes. Fourteen patients in each group (12.6%) discontinued dual therapy, mainly due to adverse events or lack of efficacy. Nine nonresponder patients received additional treatment with peginterferon/ribavirin per protocol-defined criteria. The rate of serious adverse events was low (5.9%) and varied among patients. The most common adverse events were nasopharyngitis, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST), headache, diarrhea, and pyrexia. Conclusion: Interferon-free, ribavirin-free all-oral therapy with daclatasvir and asunaprevir for 24 weeks is well tolerated and can achieve a high rate of SVR in patients with HCV genotype 1b who were ineligible, intolerant, or had not responded to prior interferon-based therapy. (Hepatology 2014;59:2083–2091)

Combination Therapy with Ombitasvir/Paritaprevir/Ritonavir for Dialysis Patients Infected with Hepatitis C Virus: A Prospective Multi-Institutional Study

“…However, this combination therapy takes 24 weeks to complete, which is twice as long as standard DAA combination therapy for patients with HCV/1b (SOF/LDV or OBV/PTV/r). In addition, combination therapy of DCV/ ASV causes liver dysfunction, headache, and pyrexia (Kumada et al 2014) at rates more frequent than combination therapy of SOF/LDV (Mizokami et al 2015) or OBV/ PTV/r . Furthermore, combination therapy of DCV/ASV was not normally used for patients with RAVs associated with resistance to NS5A inhibitors, such as Y93 or L31 mutations; combination therapy of SOF/LDV or OBV/PTV/r was found to be more efficient for these patients than DCV/ASV.…”

Efficacy and HCC development after DAA therapy for patients with chronic hepatitis C: a single center retrospective cohort study

“…Conversely, DAA therapy rarely has adverse events compared to IFN-based treatment. ASV, an NS3/4 protease inhibitor, is more likely to result in liver function test disorder [7] . In our study, 2 patients in the DCV + ASV group (n = 13) had liver function disorder [Grade 1, n = 1 (7.7%); Grade 3, n = 1 (7.7%)].…”

Efficacy and Safety of Telaprevir, Pegylated Interferon α-2b and Ribavirin Triple Therapy in Japanese Patients Infected with Hepatitis C Virus Genotype 1b

“…Recently, all-oral therapy with daclatasvir (NS5A replication complex inhibitor) plus asunaprevir (NS3 PI) was approved in Japan for patients with HCV genotype 1b who are poor candidates for IFN/RBV-based regimens. In a phase III study, SVR was achieved by 87.4% of IFN-ineligible/intolerant patients and 80.5% of prior non-responders (23). However, 13% of these patients failed treatment due to resistantassociated substitutions to both daclatasvir (predominantly NS5A-L31M/V-Y93H) and asunaprevir (predominantly NS3-D168 variants).…”